chr19-5022593-T-C

Variant names:

• chr19-5022593-T-C
• rs263063
• NM_015015.3:c.-26+6254T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015015.3(KDM4B):​c.-26+6254T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,264 control chromosomes in the GnomAD database, including 64,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64005 hom., cov: 32)
• Consequence: KDM4B NM_015015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

Genes affected

KDM4B (HGNC:29136): (lysine demethylase 4B) Enables histone H3-methyl-lysine-36 demethylase activity and histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K36 demethylation and histone H3-K9 demethylation. Located in cytosol and nucleoplasm. Implicated in autosomal dominant non-syndromic intellectual disability; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4B	NM_015015.3	c.-26+6254T>C		intron_variant	Intron 2 of 22	ENST00000159111.9	NP_055830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4B	ENST00000159111.9	c.-26+6254T>C		intron_variant	Intron 2 of 22	1	NM_015015.3	ENSP00000159111.3

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139356 AN: 152146 Hom.: 63952 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.916 AC: 139463 AN: 152264 Hom.: 64005 Cov.: 32 AF XY: 0.915 AC XY: 68100 AN XY: 74446

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.916

Alfa AF: 0.909 Hom.: 100430

Bravo AF: 0.912

Asia WGS AF: 0.855 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs263063; hg19: chr19-5022604;